New genetic loci link adipose and insulin biology to body fat distribution.

Body fat distribution is a heritable trait and a well-established predictor of adverse metabolic outcomes, independent of overall adiposity. To increase our understanding of the genetic basis of body fat distribution and its molecular links to cardiometabolic traits, here we conduct genome-wide association meta-analyses of traits related to waist and hip circumferences in up to 224,459 individuals. We identify 49 loci (33 new) associated with waist-to-hip ratio adjusted for body mass index (BMI), and an additional 19 loci newly associated with related waist and hip circumference measures (P < 5 × 10(-8)). In total, 20 of the 49 waist-to-hip ratio adjusted for BMI loci show significant sexual dimorphism, 19 of which display a stronger effect in women. The identified loci were enriched for genes expressed in adipose tissue and for putative regulatory elements in adipocytes. Pathway analyses implicated adipogenesis, angiogenesis, transcriptional regulation and insulin resistance as processes affecting fat distribution, providing insight into potential pathophysiological mechanisms

Multi-Perspective Analysis of Building Orientation Effects on Microstructure, Mechanical and Surface Properties of SLM Ti6Al4V with Specific Geometry

Building orientation is important in selective laser melting (SLM) processes. Current studies only focus on the horizontal and vertical building orientations without considering different modes of horizontal orientations. In fact, for horizontal orientation, different surfaces of the sample that contact the substrate will affect the heat transfer mode and efficiency, and in turn affect the microstructure and material properties. In this paper, the effect of two modes of horizontal building orientations on microstructure, mechanical and surface properties of SLM Ti6Al4V was studied. Current research about building orientation is deficient because the geometry of samples or test surfaces are not strictly defined, which seriously influences the results due to their different heat transfer efficiency and mode. Therefore, the geometry of the samples and test surfaces were clearly defined, and its necessity was proved in this study. To achieve the research goal, three test samples were prepared: sample SLM-PB-S with the building orientation parallel to the substrate and the shorter side L1 contacts it, sample SLM-PB-L with the building orientation parallel to the substrate and the longer side L2 contacts it and sample SLM-VB with the building orientation vertical to the substrate. Subsequently, the microstructure, grain information, densification, residual stress, micro-hardness, tensile properties and surface topography of different samples were analyzed and compared. In the results, SLM-PB-S exhibited denser microstructure and better mechanical properties than SLM-PB-L, including smaller grain size, stronger texture, higher density, micro-hardness, tensile strength, plasticity and better surface quality. It originates from a higher cooling rate and shorter scanning time between layers during SLM-PB-S fabrication, leading to finer grains, lower porosity and better interlayer metallurgical bonding, thus resulting in better material properties. This study can provide a reference to select the proper building orientation in SLM

Episodes of single-crystal material removal mode and machinability in the micro-cutting process of superalloy Inconel-718

The development tendency of miniaturization gives birth to the demand for Inconel-718 miniature parts, and micro-cutting is a promising technique to produce crystalline material miniature parts. Unfortunately, due to the non-negligible edge radius and property anisotropy, the material deformation behaviour and removal mode vary with cutting conditions, resulting in volatile machinability and inferior quality, which hinders the widespread application of Inconel-718 miniature parts. Therefore, it is urgent to clarify the evolution of material removal mode and machinability of Inconel-718 micro-cutting. Existing researches fail to consider the property anisotropy, strain-rate sensitivity and strain-rate inhomogeneity. This paper establishes strain rate-considered single-crystal micro-cutting models and performs simulations under varying cutting conditions, aiming to depict the episodes of material removal mode and machinability of Inconel-718 micro-cutting. Results show that, uncut chip thickness and cutter rake angle influence the material removal mode, and in turn influence machinability. For Inconel-718 single-crystal with [0° 0° 0°] orientation, the transition from the scratching mode to the ploughing mode is in the uncut chip thickness range of 0.2Re∼0.4Re, and the transition from the ploughing mode to the cutting mode is in the uncut chip thickness range of 0.6Re∼0.8Re or the rake angle range of −30°∼-15°. In comparison, cutting speed and clearance angle have little effect on material removal mode. Cutting speed influences the strain rate of the cutting-affected zone, and in turn influences machinability. The maximum strain rate of the cutting-affected zone is respectively around 0.45 s−1 and 10,960 s−1 under the cutting speeds of 2Re/s and 20000Re/s

Hpa1 is a type III translocator in Xanthomonas oryzae pv. oryzae

Abstract Background Pathogenic Gram-negative bacteria interact with their eukaryotic hosts by deploying the type III translocon to inject effector proteins into the cytosol of eukaryotic cells. The translocon compositions, the number and biochemical characteristics of type III translocators in animal-pathogenic bacteria have been well elucidated, but information is lacking for plant-pathogenic bacteria. With extensive studies on biological functions of the Hpa1 protein secreted by the type III secretion system in Xanthomonas oryzae pv. oryzae (Xoo), we show here that Hpa1 is a type III translocator based on measurements of two proteins categorized as transcription activator-like (TAL) effector. Results Hpa1 was functionally associated with the TAL effector PthXo1 or AvrXa10 by genetic analysis of the wild-type Xoo strain and related mutants or recombinant strains. Inoculation experiments suggested that Hpa1 is required not only for the virulent role of PthXo1 in the susceptible rice variety Nipponbare, but also for the avirulent function of AvrXa10 on the resistant rice variety IRBB10. Hpa1 is unrelated to the secretion of PthXo1 and AvrXa10 out of bacterial cells. However, Hpa1 is critical for both TAL effectors to be translocated from bacterial cells into the cytosol of rice cells based on replicate experiments performed on the susceptible and resistant varieties, respectively. Hpa1-mediated translocation of PthXo1 is coincident with induced expression of rice SWEET11 gene, which is the regulatory target of PthXo1, resulting in the occurrence of the bacterial blight disease in the susceptible rice variety. By contrast, the immune hypersensitive response is induced in agreement with induced expression of rice Xa10 gene, which is the target of AvrXa10, only when AvrXa10 is translocated from bacteria into cells of the resistant rice variety. All the virulent or avirulent performances of the TAL effectors are nullified by directed mutation that removes the α-helix motif from the Hpa1 sequence. Conclusions The genetic and biochemical data demonstrate that Hap1 is a type III translocator at least for TAL effectors PthXo1 and AvrXa10. The effect of the directed mutation suggests that Hpa1 depends on its α-helical motif to fulfil the translocator function

The Protein Composition Changed the Quality Characteristics of Plant-Based Meat Analogues Produced by a Single-Screw Extruder: Four Main Soybean Varieties in China as Representatives

Plant-based meat analogues (PBMs) are increasingly interesting to customers because of their meat-like quality and contribution to a healthy diet. The single-screw extruder is an important method for processing PBMs, and the characteristics of the product are directly affected by the composition of the raw materials; however, little research focuses on this issue. To explore the effect of protein composition on the quality characteristics of PBMs produced by a single-screw extruder, four soybean varieties used in China (Heihe 43 (HH 43), Jiyu 86 (JY 86), Suinong 52 (SN 52), and Shengfeng 5 (SF 5)) were selected. The 11S/7S ratios for these varieties ranged from 1.0: 1 to 2.5: 1 in order to produce PBMs with different protein compositions. The structure, processing, nutrition, and flavor characteristics were explored to analyze their differences. The results showed that protein composition affected the structure of PBMs, but the correlation was not significant. Meanwhile, a lower 11S/7S ratio (HH 43) did not prove to be a favorable characteristic for the processing of PBMs. From the perspective of nutrition and flavor, it seems acceptable to use a moderate 11S/7S ratio (JY 86 and SN 43) to produce PBMs. This study proved that the protein composition of raw materials affects the characteristics of PBM products produced by a single-screw extruder. To produce PBMs of higher quality, soybeans with a markedly different 11S/7S ratio should not be selected

Histamine Is Responsible for the Neuropathic Itch Induced by the Pseudorabies Virus Variant in a Mouse Model

Pseudorabies virus (PRV) is the causative agent of pseudorabies (PR). It can infect a wide range of mammals. PRV infection can cause severe acute neuropathy (the so-called “mad itch”) in nonnatural hosts. PRV can infect the peripheral nervous system (PNS), where it can establish a quiescent, latent infection. The dorsal root ganglion (DRG) contains the cell bodies of the spinal sensory neurons, which can transmit peripheral sensory signals, including itch and somatic pain. Little attention has been paid to the underlying mechanism of the itch caused by PRV in nonnatural hosts. In this study, a mouse model of the itch caused by PRV was elaborated. BALB/c mice were infected intramuscularly with 105 TCID50 of PRV TJ. The frequency of the bite bouts and the durations of itch were recorded and quantified. The results showed that the PRV-infected mice developed spontaneous itch at 32 h postinfection (hpi). The frequency of the bite bouts and the durations of itch were increased over time. The mRNA expression levels of the receptors and the potential cation channels that are relevant to the itch-signal transmission in the DRG neurons were quantified. The mRNA expression levels of tachykinin 1 (TAC1), interleukin 2 (IL-2), IL-31, tryptases, tryptophan hydroxylase 1 (TPH1), and histidine decarboxylase (HDC) were also measured by high-throughput RNA sequencing and real-time reverse transcription PCR. The results showed that the mean mRNA level of the HDC in the DRG neurons isolated from the PRV-infected mice was approximately 25-fold higher than that of the controls at 56 hpi. An immunohistochemistry (IHC) was strongly positive for HDC in the DRG neurons of the PRV-infected mice, which led to the high expression of histamine at the injected sites. The itch of the infected mice was inhibited by chlorphenamine hydrogen maleate (an antagonist for the histamine H1 receptor) in a dose-dependent manner. The mRNA and protein levels of the HDC in the DRG neurons were proportional to the severity of the itch induced by different PRV strains. Taken together, the histamine synthesized by the HDC in the DRG neurons was responsible for the PRV-induced itch in the mice

SOCS3 is Related to Cell Proliferation in Neuronal Tissue: An Integrated Analysis of Bioinformatics and Experiments

Glioma is the most common primary malignant tumor that occurs in the central nervous system. Gliomas are subdivided according to a combination of microscopic morphological, molecular, and genetic factors. Glioblastoma (GBM) is the most aggressive malignant tumor; however, efficient therapies or specific target molecules for GBM have not been developed. We accessed RNA-seq and clinical data from The Cancer Genome Atlas, the Chinese Glioma Genome Atlas, and the GSE16011 dataset, and identified differentially expressed genes (DEGs) that were common to both GBM and lower-grade glioma (LGG) in three independent cohorts. The biological functions of common DEGs were examined using NetworkAnalyst. To evaluate the prognostic performance of common DEGs, we performed Kaplan-Meier and Cox regression analyses. We investigated the function of SOCS3 in the central nervous system using three GBM cell lines as well as zebrafish embryos. There were 168 upregulated genes and 50 downregulated genes that were commom to both GBM and LGG. Through survival analyses, we found that SOCS3 was the only prognostic gene in all cohorts. Inhibition of SOCS3 using siRNA decreased the proliferation of GBM cell lines. We also found that the zebrafish ortholog, socs3b, was associated with brain development through the regulation of cell proliferation in neuronal tissue. While additional mechanistic studies are necessary, our results suggest that SOCS3 is an important biomarker for glioma and that SOCS3 is related to the proliferation of neuronal tissue